title: Diet-induced obesity may affect the uterine immune environment in early-mid pregnancy, reducing NK-cell activity and potentially compromising uterine vascularization.
abstract: OBJECTIVE
  To investigate the effect of obesity in early-mid pregnancy on crucial pregnancy hormones and the uterine immune environment.
  
  
  BACKGROUND
  Obesity impacts reproductive ability, adversely affecting conception and leading to complications in pregnancy. Obesity is often regarded as a stress state and an immune disease, both of which may contribute to pregnancy failure. We previously demonstrated that stress in early pregnancy greatly alters progesterone secretion. As progesterone is an immunomodulator, altered progesterone secretion may adversely modify the maternal immune system. In the current study, we test the hypothesis that obesity during pregnancy adversely alters the uterine immune environment.
  
  
  METHODS
  An obese mouse model was created by feeding C57/BL6 mice on a high-fat (HF)/sugar diet for 12 weeks before pregnancy. Control mice were fed on lower-fat/sugar chow. Mice were mated, and on day 7.5 of pregnancy plasma progesterone and prolactin were measured by immunoassay. Cells from the uterus-draining inguinal lymph nodes were collected for analysis of the uterine immune response by flow cytometry.
  
  
  RESULTS
  Diet-induced obesity increased the secretion of progesterone and altered a number of uterine natural killer (NK)- and T-cell responses. These included a marked reduction in the percentage of leucocyte-derived NK cells and reduced expression of interferon-γ (IFN-γ) in the NK cells compared with control mice.
  
  
  CONCLUSIONS
  Maternal obesity, induced by an HF diet, may lead to a reduction in the expression of IFN-γ in NK cells. NK-cell-derived IFN-γ is reported to be involved in supporting uterine spiral artery remodelling. Thus, obesity in early pregnancy may compromise vascularization by reducing the expression of IFN-γ-positive NK cells. Furthermore, the expression of uterine CD8(+) cells was reduced in the HF diet-fed mice, suggesting obesity may adversely alter the maternal immune adaptation that is essential for effective pregnancy.
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.
authors.forename: V J
authors.initials: VJ
authors.lastname: Parker
authors.affiliation: Laboratory for Experimental Feto-Maternal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: M E
authors.initials: ME
authors.lastname: Solano
authors.affiliation: Laboratory for Experimental Feto-Maternal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: P C
authors.initials: PC
authors.lastname: Arck
authors.affiliation: Centre for Integrative Physiology, University of Edinburgh, Edinburgh, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Douglas
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D005333:Fetus / Q000276:immunology; D018507:Gene Expression Regulation, Developmental; D007108:Immune Tolerance; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism*; D008431:Maternal-Fetal Exchange; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000150:complications / Q000276:immunology / Q000473:pathology*; D011247:Pregnancy; D011374:Progesterone / Q000378:metabolism*; D014599:Uterus / Q000276:immunology / Q000473:pathology*
chemical_list: D011374:Progesterone; D007371:Interferon-gamma